Johnson & Johnson announced new analyses from the Phase 3 MARIPOSA study demonstrating that first-line treatment with RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE® (lazertinib) significantly reduces the development of epidermal growth factor receptor (EGFR)- and MET-driven resistance compared with osimertinib in patients with EGFR-mutated non-small cell lung cancer (NSCLC) with exon 19 deletion (ex19del) or L858R mutations (Poster Abstract PT1.03).

These findings, presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Congress on Lung Cancer (WCLC), build upon the combination’s previously reported survival advantage of more than four years in a chemotherapy-free regimen—exceeding the median observed with osimertinib by one year. Together, the data underscore the potential of RYBREVANT® plus LAZCLUZE® to transform disease biology by preventing acquired resistance.

Resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, remains a major barrier to long-term control of EGFR-mutated NSCLC. In MARIPOSA, MET amplification occurred in only three percent of patients receiving the RYBREVANT® combination versus 13 percent with osimertinib (P=0.002). Similarly, secondary EGFR mutations, including C797S, were markedly lower with the combination (1 percent vs. 8 percent; P=0.01). Patients on osimertinib were also more likely to discontinue treatment early due to resistance, with 23 percent discontinuing within six months compared to only four percent on the combination.

“We now have compelling evidence that TKI monotherapy is no longer sufficient in the first-line treatment of EGFR-mutated lung cancer,” said Professor Sanjay Popat, FRCP, Ph.D., medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research, UK. “The MARIPOSA results confirm that combining RYBREVANT with LAZCLUZE reduces EGFR- and MET-driven resistance, delivering a longer and stronger first response.”

Johnson & Johnson underscored that the combination’s safety profile remained consistent with prior analyses, with most adverse events (AEs) occurring early and no new safety signals observed. Preventive measures, such as preemptive skin care, were shown to help manage the most common side effects.

“Choosing the first treatment for EGFR-mutated NSCLC is one of the most important decisions we make, as it shapes the disease course,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Leader, Johnson & Johnson Innovative Medicine. “These data highlight how RYBREVANT plus LAZCLUZE blocks key resistance pathways, keeping future treatment options open and extending survival—benefits not seen with prior therapies.”

RYBREVANT® plus LAZCLUZE® is already approved in the United States, Europe and other global markets for patients with first-line EGFR-mutated NSCLC, based on the MARIPOSA study results.